Oxidation and isomerization of delta5-3beta-hydroxysteroids to delta4-3-ketosteroids are reactions catalyzed by the enzyme 3beta-hydroxysteroid dehydrogenase (delta5-delta4)-isomerase (3betaHSD-isomerase) in all steroidogenic tissues. Although 3betaHSD-isomerase has been the subject of many studies, much uncertainty remains about fundamental characteristics of this important enzyme. This application proposes a set of cellular studies designed to examine the effects of end-product steroids and the mechanism(s) by which these hormones act to regulate 3betaHSD-isomerase. Also, the investigator proposes to examine, in the future, regulatory factors in the genome that mediate the ability of hormones to regulate the expression of 3betaHSD-isomerase. The specific objectives of this proposal are to test the hypothesis that 1) the negative and positive effects of gonadal steroids on adrenal and Leydig cells are receptor mediated, and 2) that receptor mediated action of the steroids alters the synthesis of 3betaHSD-isomerase. Cell culture and steroid receptor agonists and antagonists will be used to examine the response of 3betaHSD-isomerase to end-product steroid treatment.